抗肿瘤坏死因子-α单克隆抗体对阻塞性黄疸大鼠肝脏保护作用的实验研究

    Experimental study about the protective effect of anti-TNF-α McAb on liver of rats with obstructive jaundice

    • 摘要: 目的: 探讨肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)在阻塞性黄疸大鼠肝损伤中的作用及抗肿瘤坏死因子-α单克隆抗体(anti-TNF-αMcAb)的保护作用。方法: 将雄性SD大鼠24只随机分为胆总管结扎组(BDL)、BDL+anti-TNF-αMcAb组、假手术组(SO)。BDL+anti-TNF-αMcAb组治疗于胆总管结扎后第3天开始经尾静脉注射anti-TNF-αMcAb (1 mg/kg),连用5天;BDL组和SO组以同样的方法注射等量的生理盐水。分别检测各组大鼠血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)和TNF-α水平,并在光镜和电镜下观察各组大鼠肝组织的病理变化。结果: BDL组及BDL+anti-TNF-αMcAb治疗组大鼠血清ALT、AST和TNF-α水平均高于SO组(P<0.01),但BDL+anti-TNF-αMcAb治疗组增高的程度均低于BDL组(P<0.05~P<0.01),并且肝组织病理改变也较轻。SO组肝组织无明显病理改变。结论: TNF-α可能是阻塞性黄疸时肝损伤的重要介导因子,使用抗肿瘤坏死因子-α单克隆抗体,可以减轻阻塞性黄疸时肝损伤。

       

      Abstract: Objective: To investigate the role of tumor necrosis factor-α(TNF-α) in liver damage in rats with obstructive jaundice and the protective effect of anti-TNF-αMcAb.Methods: Twenty-four male Sprague-Dawley rats were randomly divided into three groups:bile duct-ligation(BDL) group,bile duct-ligation+anti-TNF-αMcAb(BDL+anti-TNF-αMcAb) group and sham-operation(SO) group.BDL+anti-TNF-αMcAb group was subjected to damage with intravenous administration of anti-TNF-αMcAb(1mg/kg) for five days,starting from the 3rd day after bile duct-ligation;BDL group and SO group were administered with saline in the same manner.The levels of serum alanine amiotransferase(ALT),aspartate aminotransferase(AST) and TNF-α were detected in each group.The histopathology was observed by light and electron microscopy in the liver of rats with obstructive jaundice.Results: The levels of serum ALT,AST and TNF-α in BDL group and BDL+anti-TNF-αMcAb group were markedly higher than those in SO group(P<0.01),and the levels of serum ALT,AST and TNF-α in BDL+anti-TNF-αMcAb group were much lower than those in BDL group(P<0.05 to P<0.01),the changes of liver histopathology were minor in BDL+anti-TNF-αMcAb group.SO group had no apparent change.Conclusions: TNF-α may be one of the most important mediators in live damage induced by obstructive jaundice,and the use of anti-TNF-αMcAb can relieve the liver damage.

       

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